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Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons.

Kirby ED, Friedman AR, Covarrubias D, Ying C, Sun WG, Goosens KA, Sapolsky RM, Kaufer D - Mol. Psychiatry (2011)

Bottom Line: We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not.Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis.These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons.

View Article: PubMed Central - PubMed

Affiliation: Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA.

ABSTRACT
Impaired regulation of emotional memory is a feature of several affective disorders, including depression, anxiety and post-traumatic stress disorder. Such regulation occurs, in part, by interactions between the hippocampus and the basolateral amygdala (BLA). Recent studies have indicated that within the adult hippocampus, newborn neurons may contribute to support emotional memory, and that regulation of hippocampal neurogenesis is implicated in depressive disorders. How emotional information affects newborn neurons in adults is not clear. Given the role of the BLA in hippocampus-dependent emotional memory, we investigated whether hippocampal neurogenesis was sensitive to emotional stimuli from the BLA. We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not. Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis. We also show that BLA lesions prevent selective activation of immature newborn neurons in response to a fear-conditioning task. These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons. Together, these findings denote functional implications for proliferation and recruitment of new neurons into emotional memory circuits.

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Bilateral BLA lesions suppressed hippocampal neurogenesis(a) Experimental timeline. (b) Bilaterally lesioned rats (n = 5) had significantly fewer PCNA positive cells than sham operated rats (n =6). *p<0.05. (c) Bilaterally lesioned rats also had significantly fewer BrdU positive cells than sham operated rats, representing a reduction in the number of 5-10 day old cells. *p<0.05. (d) BLA lesion did not affect the percent of BrdU positive cells expressing one of three cell fate markers: doublecortin (DCX), S100β or myelin basic protein (MBP). (e) Representative confocal images showing colocalization of BrdU with DCX, S100β or MBP. Scale bar = 10 μm.
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Figure 2: Bilateral BLA lesions suppressed hippocampal neurogenesis(a) Experimental timeline. (b) Bilaterally lesioned rats (n = 5) had significantly fewer PCNA positive cells than sham operated rats (n =6). *p<0.05. (c) Bilaterally lesioned rats also had significantly fewer BrdU positive cells than sham operated rats, representing a reduction in the number of 5-10 day old cells. *p<0.05. (d) BLA lesion did not affect the percent of BrdU positive cells expressing one of three cell fate markers: doublecortin (DCX), S100β or myelin basic protein (MBP). (e) Representative confocal images showing colocalization of BrdU with DCX, S100β or MBP. Scale bar = 10 μm.

Mentions: Adult hippocampal neurogenesis is a multi-phase process regulated by the proliferation, differentiation, migration, and survival of new cells23. To assess the effect of loss of BLA input on the neurogenic process, we excitotoxically lesioned the BLA of adult male rats bilaterally28, 31 (Figure 1) and investigated cell proliferation as well as differentiation (Figure 2a). BLA lesion reduced the number of proliferation cell nuclear antigen (PCNA) positive cells by 55.9% compared to rats who received bilateral sham surgery (Figure 2b). BLA-lesion also led to a 45.3% reduction in the number of BrdU positive dentate gyrus cells 5-10 days after proliferative cells were labeled by BrdU injection (Figure 2c). These results indicate suppression of cell proliferation following BLA lesion, resulting in a persistent reduction in immature cells. BLA lesion did not affect cell fate, with approximately 85-90% of new cells expressing the neural marker doublecortin (DCX) and less than 5% expressing the astrocytic marker S100β or the oligodendrocyte marker myelin basic protein (MBP) regardless of lesion (Figure 2d-e). These data indicate that BLA lesions cause a reduction in the pool of immature neurons and glia three weeks after lesion.


Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons.

Kirby ED, Friedman AR, Covarrubias D, Ying C, Sun WG, Goosens KA, Sapolsky RM, Kaufer D - Mol. Psychiatry (2011)

Bilateral BLA lesions suppressed hippocampal neurogenesis(a) Experimental timeline. (b) Bilaterally lesioned rats (n = 5) had significantly fewer PCNA positive cells than sham operated rats (n =6). *p<0.05. (c) Bilaterally lesioned rats also had significantly fewer BrdU positive cells than sham operated rats, representing a reduction in the number of 5-10 day old cells. *p<0.05. (d) BLA lesion did not affect the percent of BrdU positive cells expressing one of three cell fate markers: doublecortin (DCX), S100β or myelin basic protein (MBP). (e) Representative confocal images showing colocalization of BrdU with DCX, S100β or MBP. Scale bar = 10 μm.
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Related In: Results  -  Collection

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Figure 2: Bilateral BLA lesions suppressed hippocampal neurogenesis(a) Experimental timeline. (b) Bilaterally lesioned rats (n = 5) had significantly fewer PCNA positive cells than sham operated rats (n =6). *p<0.05. (c) Bilaterally lesioned rats also had significantly fewer BrdU positive cells than sham operated rats, representing a reduction in the number of 5-10 day old cells. *p<0.05. (d) BLA lesion did not affect the percent of BrdU positive cells expressing one of three cell fate markers: doublecortin (DCX), S100β or myelin basic protein (MBP). (e) Representative confocal images showing colocalization of BrdU with DCX, S100β or MBP. Scale bar = 10 μm.
Mentions: Adult hippocampal neurogenesis is a multi-phase process regulated by the proliferation, differentiation, migration, and survival of new cells23. To assess the effect of loss of BLA input on the neurogenic process, we excitotoxically lesioned the BLA of adult male rats bilaterally28, 31 (Figure 1) and investigated cell proliferation as well as differentiation (Figure 2a). BLA lesion reduced the number of proliferation cell nuclear antigen (PCNA) positive cells by 55.9% compared to rats who received bilateral sham surgery (Figure 2b). BLA-lesion also led to a 45.3% reduction in the number of BrdU positive dentate gyrus cells 5-10 days after proliferative cells were labeled by BrdU injection (Figure 2c). These results indicate suppression of cell proliferation following BLA lesion, resulting in a persistent reduction in immature cells. BLA lesion did not affect cell fate, with approximately 85-90% of new cells expressing the neural marker doublecortin (DCX) and less than 5% expressing the astrocytic marker S100β or the oligodendrocyte marker myelin basic protein (MBP) regardless of lesion (Figure 2d-e). These data indicate that BLA lesions cause a reduction in the pool of immature neurons and glia three weeks after lesion.

Bottom Line: We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not.Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis.These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons.

View Article: PubMed Central - PubMed

Affiliation: Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA.

ABSTRACT
Impaired regulation of emotional memory is a feature of several affective disorders, including depression, anxiety and post-traumatic stress disorder. Such regulation occurs, in part, by interactions between the hippocampus and the basolateral amygdala (BLA). Recent studies have indicated that within the adult hippocampus, newborn neurons may contribute to support emotional memory, and that regulation of hippocampal neurogenesis is implicated in depressive disorders. How emotional information affects newborn neurons in adults is not clear. Given the role of the BLA in hippocampus-dependent emotional memory, we investigated whether hippocampal neurogenesis was sensitive to emotional stimuli from the BLA. We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not. Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis. We also show that BLA lesions prevent selective activation of immature newborn neurons in response to a fear-conditioning task. These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons. Together, these findings denote functional implications for proliferation and recruitment of new neurons into emotional memory circuits.

Show MeSH
Related in: MedlinePlus